Tributyl O-acetylcitrate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1992

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1992

Materials and methods

Objective of study:

other: ADME

Test guideline

Guideline:

other: not further specified

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Test material form:

not specified

Details on test material:

Name of test material (as cited in study report): Acetyl tributyl citrate (CAS RN 77-90-7)
Analytical purity: 99.02 %
Radiochemical purity (if radiolabelling): 100 %

Radiolabelling:

yes

Remarks:

14C

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

Absorption and elimination study: 4 m
Rate of absorption study: 5 m

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Duration and frequency of treatment / exposure:

single oral dosing

Doses / concentrations

Remarks:

Doses / Concentrations:
70 mg [14C]ATBC/kg bw

No. of animals per sex per dose / concentration:

4 - 5

Control animals:

not specified

Details on dosing and sampling:

Urine, faeces, cage wash, expired organics and [14C]CO2, blood, tissues (including GI tract and contents) and carcass were analysed for [14C] and/or unchanged ATBC

Statistics:

no data

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

see below

Details on distribution in tissues:

see below

Details on excretion:

see below

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

At least 9 radiolabeled metabolites were found in urine and 3 in faeces. Urinary metabolites positively identified were acetyl citrate, mono-butyl citrate (tentatively the major metabolite), acetyl mono-butyl citrate, dibutyl citrate, and acetyl dibutyl citrate.

Any other information on results incl. tables

Absorption of dosed [14C] was rapid (t1/2 = 1.0 h) and extensive (>= 67 %). Absorbed [14C]ATBC was rapidly and completely metabolized and eliminated. More than 87 % of the administered radioactivity was excreted during the initial 24 hrs after dosing. For [14C] in blood an elimination half-life of 3.4 hrs was calculated during this interval. Less than 1 % of the dosed radioactivity remained in tissues and carcass 48 hrs post-dosing.

The principle route of [14C] excretion was via urine (59 – 70 % of the [14C] dose), while 25 – 36 % were excreted via faeces and 2 % as [14C]CO2.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
After oral gavage, ATBC is rapidly absorbed, metabolized and excreted by rats.

Executive summary:

In this study groups of 4 – 5 male Sprague-Dawley rats were dosed once via gavage with 70 mg [14C]ATBC/kg bw and urine, faeces, cage wash, expired organics and [14C]CO2, blood, tissues (including GI tract and contents) and carcass were analysed for [14C] and/or unchanged ATBC.

Absorption of dosed [14C] was rapid (t1/2 = 1.0 h) and extensive (>= 67 %). Absorbed [14C]ATBC was rapidly and completely metabolized and eliminated. More than 87 % of the administered radioactivity was excreted during the initial 24 hrs after dosing. For [14C] in blood an elimination half-life of 3.4 hrs was calculated during this interval. Less than 1 % of the dosed radioactivity remained in tissues and carcass 48 hrs post-dosing.

The principleroute of [14C] excretion was via urine (59 – 70 % of the [14C] dose), while 25 – 36 % were excreted via faeces and 2 % as [14C]CO2. At least 9 radiolabeled metabolites were found in urine and 3 in faeces. Urinary metabolites positively identified were acetyl citrate, mono-butyl citrate (tentatively the major metabolite), acetyl mono-butyl citrate, dibutyl citrate, and acetyl dibutyl citrate.

It was concluded that the low oral toxicity of ATBC is not due to poor absorption but is caused by an intrinsic property of ATBC and/or its metabolites or is due to rapid clearance in the rat.